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A. Macrolide Generationsnavigator

  1. First: Erythromycin, (Clindamycin)
  2. Second: Clarithromycin, Azithromycin, Dirithromycin

B. Erythromycinnavigator

  1. Good coverage of staphylococcus (not MRSA) and streptococcus and Campylobacter
  2. Excellent for mycoplasma; poor against H. influenza
  3. High dose effective for Legionnaire's Disease (L. pneumophila)
  4. Dose
    1. Standard: 500mg qid IV or po
    2. High ("Legionella") Dose 1gm IV qid
  5. Side effects very common
    1. High incidence of nausea, vomiting
    2. High dose IV causes venous sclerosis, hepatitis
    3. Associated with QTc prolongation and sudden cardiac death with 2X increased risk [11]
    4. Concomitant use of erythromycin and CYP3A4 inhibitors 5X increased risk of death [11]
  6. Caution when used with theophylline, carbamazepine, and other protein bound drugs
  7. Do not use with diltiazem, verapamil, imidazole antifungals, troleandomycin [11]

C. Clindamycin (Cleocin®) navigator

  1. Excellent anaerobic coverage (except B. fragilis )
  2. Good staphylococcus (not MRSA) and streptococcus coverage
  3. Also used in combination therapy, treatment for toxoplasmosis, pneumocystis
  4. Dose: IV 600mg tid, PO 300-600mg tid - qid
  5. Associated with high risk of pseudomembranous colitis due to C. difficile
    1. Use of clindamycin increases resistance and risk of large diarrheal outbreaks [8]
    2. Clindamycin use in hospital should be restricted (prevents outbreaks)

D. Clarithromycin (Biaxin®) navigator

  1. Spectrum is similar to a combination of ß-lactam and erythromycin
  2. Effective against many typical and atypical organisms
    1. Streptococci
    2. Some Staphylococci
    3. Moraxella catarrhalis
    4. Haemophilus influenzae
    5. Legionella
    6. Mycoplasma
    7. Chlamydia
    8. Borrelia burgdorferi
  3. Potent activity against Helicobacter pylori
  4. Excellent activity against Mycobacterium avium-intracellulare (MAI)
  5. Dose: 250-500mg po bid
  6. Few side effects, with mild nausea (infrequent)
  7. Clarithromycin or azithromycin use for streptococcal pharyngitis associated with increased carriage of macrolide resistant streptococcus [2]

E. Azithromycin (Zithromax®, Zmax®)navigator

  1. Enhanced H. influenza and M. cattharalis coverage compared to erythromycin
  2. May be useful for Salmonella infections and MAI
  3. Effective against many typical and atypical organisms
    1. Streptococci
    2. Some Staphylococci
    3. Moraxella catarrhalis
    4. Haemophilus influenzae
    5. Legionella
    6. Mycoplasma
    7. Chlamydia - including species causing trachoma [12]
    8. Borrelia burgdorferi
    9. Cholera (Vibrios cholerae)
    10. Prevention of pneumocystis infection in HIV+ patients with MAI [7]
  4. Sexually Transmitted Diseases (STD)
    1. Excellent activity against N. gonorrhoea (drug concentrated within cells)
    2. Syphilis [6] - single 1gm dose prevents transmission of syphilis
    3. Chlamydia trachomatis - single 1gm dose is now FDA approved for GU infections
    4. Non-gonococcal urethritis
    5. Chancroid (Haemophilus ducrei)trachomatis
  5. May be used for COPD exacerbations and in acute bronchitis
  6. Azithromycin for 3 months after initial myocardial infarction had no effect on secondary coronary events in patients with evidence of C. pneumoniae infection [9]
  7. In cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, oral azithromycin for 5 months improves FEV1, reduces exacerbations, increases weight []
  8. Dose
    1. Usual dosing Zithromax 500mg x 1d then 250mg x 4d po (qd dose)
    2. Single 1gm dose Zithromax is effective against essentially all of the STDs [6]
    3. Extended release azithromycin (Zmax®) 2gm single dose on empty stomach for most indications, FDA approved for community aquired pneumonia and acute sinusitis [13]
    4. Oral single dose azithromycin (1gm) superior to single dose ciprofloxacin (1gm) in areas of quinolone resistance in adults [14]
  9. One to three doses (1gm) eradicates >93% of infections in endemic areas [5]
  10. Clarithromycin or azithromycin use for streptococcal pharyngitis associated with increased carriage of macrolide resistant streptococcus [2]

F. Dirithromycin (Dynabac®) [3]navigator

  1. Active against Streptococci, M. catarrhalis, Legionella, atypicals, and Staphylococci
  2. Now also approved for use in H. influenza infections
  3. Indicated for COPD exacerbations as well for acute bronchitis (bacterial etiology only)
  4. Dose is 500mg po qd (supplied as 250mg tablets)
  5. Side effects may be similar to erythromycin, but reduced daily dosing is advantage
  6. Not metabolized by P450 system so reduced likelihood of drug-drug interactions

G. Drug Interactions [4]navigator

  1. Antihistamines
    1. Increase serum half-life of terfenadine (Seldane®) and astemizole (Hismanal®)
    2. This may lead to prolongation of the QTc interval and Torsade des Pointes
    3. Terfenadine (Seldane®) has now been withdrawn from the market
  2. Benzodiazepines - reduced metabolism, increased sedation
  3. Carbamazepine (Tegretol®) - toxicity
  4. Cisapride (Propulsid®) - increased QTcx interval and Torsade des Pointes
  5. Clozapine (Clozaril®) - reduced metablism, seizures
  6. Cyclosporine (CsA, Sandimmune®) - increased levels, azotemia
  7. Digitalis - reduced metabolism, digitalis toxicity
  8. Ergot alkaloids - hypertension, vasospasm
  9. Pimozide - sudden death
  10. Tacrolimus (FK506) - increased levels, azotemia
  11. Theophylline - increased theophylline levels, toxicity
  12. Warfarin (Coumadin®) - enhanced anticoagulation
  13. Drug Metabolism
    1. Macrolides are metabolized by liver
    2. Doses should be reduced in severe liver disease
    3. May wish to avoid these agents in patients with liver disease
    4. No dose reductions are need in most patients with renal disease

References navigator

  1. Macrolides. 1992. Med. Let. 34(870):45
  2. Malhotra-Kumar S, Lammens C, Coenen S, et al. 2007. Lancet. 369(9560):482 abstract
  3. Dirithromycin. 1995. Med Let. 37(962):109 abstract
  4. Gregg CR. 1999. Am J Med. 106(2):227 abstract
  5. Schachter J, West SK, Mabey D, et al. 1999. Lancet. 354(9179):630 abstract
  6. Hook EW III, Stephens J, Ennis DM. 1999. Ann Intern Med. 131(6):434 abstract
  7. Dunne MW, Bozzette S, McCutchan JA, et al. 1999. Lancet. 354(9182):891 abstract
  8. Johnson S, Samore MH, Farrow KA, et al. 1999. NEJM. 341(22):1645 abstract
  9. O'Connor CM, Dunne MW, Pfeffer MA, et al. 2003. JAMA. 290(11):1459 abstract
  10. Saiman L, Marshall BC, Mayer-Hamblett N, et al. 2003. JAMA. 290(13):1749 abstract
  11. Ray WA, Murray KT, Meredith S, et al. 2004. NEJM. 351(11):1089 abstract
  12. Solomon AW, Holland MJ, Alexander NDE, et al. 2004. NEJM. 351(19):1962 abstract
  13. Azithromycin Extended Release. 2005. Med Let. 47(1218):78 abstract
  14. Saha D, Karim MM, Khan WA, et al. 2006. NEJM. 354(23):2452 abstract